One of the most complex and difficult problems that has plagued the medical profession and pharmaceutical industry for decades is the problem of achieving a therapeutic concentration of a drug locally at a target site within the body without producing unwanted systemic side effects. Parenteral or oral therapy of substances directed at treating disease in a particular internal organ must often be given in amounts dependent upon achieving critical systemic blood levels that may produce devastating side effects in other areas of the body. A prime example of a situation where local therapy is needed with drugs that also produce unwanted systemic side effects is the prevention of complications following the placement of a cardiovascular prosthetic device such as a prosthetic vascular graft or a patch used to repair a damaged vessel.
Graft failure is often associated with the inherent thrombogenicity of the blood contacting surface of the prosthetic device and with the body's own repair mechanisms which may lead to progressive stenotic occlusion due to neointimal fibrosis and hyperplasia. Systemic therapy aimed at preventing coagulation and thrombosis locally at the graft site is often complicated by bleeding that may occur at other sites. Likewise, systemic treatment with growth mediators or chemotherapeutic agents may produce a hyperplastic or hypoplastic response in tissue not specifically targeted. Similarly, the local administration of vasodilators may produce systemic hypotension.
There have been many attempts to render vascular grafts less thrombogenic, e.g., by coating the luminal surface of the graft with non-thrombogenic polymers, cells, or with anticoagulant drugs in a polymer coating. Although some improvements in graft performance have been achieved, complications with clotting, thrombosis, and restenosis, especially due to fibroplasia and smooth muscle proliferation, still abound.
Other attempts to improve graft performance have provided vascular grafts or patches having a tubular drug port attached to a drug reservoir around a macroporous graft. However, such methods do not uniformly deliver drugs to the locations in need, especially when low infusion rates are being utilized.
Some grafts are provided for local delivery of drugs as mentioned above, but such grafts typically include an integrated pump/reservoir that do not allow for the separation of the pump/reservoir when it is no longer needed, to allow for maintenance or repositioning, etc.